tbuckley/cabot-search huggingface dataset:
P1002: ANTI-FIBROTIC ACTIVITY OF BMP2 IN BONE MARROW-DERIVED MESENCHYMAL STROMAL CELLS OF MYELOPROLIFERATIVE NEOPLASMS
Authors: T. Subotički, E. Živković, O. Mitrović Ajtić, M. Vukotić, D. Đikić, T. Dragojević, D. Šefer, S. Bižić, J. F. Santibanez, M. Gotić, V. P. Čokić
Journal: HemaSphere (2022)

Background: Myeloproliferative neoplasms (MPN) are clonal hematopoietic disorders that include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Bone marrow fibrosis (BMF) is a shared feature of all MPN, although it is most pronounced in PMF and represents a major diagnostic criteria. Studies suggest a correlation between the grade of BMF and prognosis of MPN, with more fibrosis associated with worse outcome. A large body of evidence has suggested that transforming growth factor beta (TGF-β) is among the most prominent inducers of fibrotic processes. Bone morphogenetic proteins (BMPs) are major regulators of cell fate in tissue homeostasis. In MPN, bone marrow-derived mesenchymal stromal cells (BM-MSC) are identified as a major cellular source of fibrosis, but exact molecular mechanism involved have not been identified so far. Aims: In addition to apoptosis and prolifration, we analyzed the effect of BMP2 and TGF- β / SMAD signaling pathway on the fibrotic phenotype of BM-MSC isolated from MPN patients and healthy donors. Methods: Bone marrow aspirates from 5 newly diagnosed MPN patients (3 PMF and 2 PV patients) and 3 healthy donors were analyzed by immunofluorescence expression of fibronectin and alpha smooth muscle Actin (αSMA), after treatment with TGF-β and / or BMP2. Using immunocytochemistry, we analyzed HEL 92.1.7 cells with a homozygous expression of JAK2V617F for proliferation (Ki67) and apoptosis (ssDNA) during exposure to BMP2 and selective BMP signaling inhibitor LDN-193189. Results: Our results showed that TGF-β significantly increased fibronectin expression, in contrast to BMP2, in BM-MSC of healthy donors. Also, the joint treatment of TGF-β and BMP2 reduced the level of fibronectin expression relative to TGF-β. In addition, TGF-β increased αSMA expression in BM-MSC from healthy donors. In contrast, BMP2 reduces the expression of αSMA and fibronectin in BM-MSC of healthy donors.BMP2 significantly reduced fibronectin expression in BM-MSC compared to untreated cells of patients with MPN. BMP2 dose dependently and significantly (p<0.01) increased the proliferation of HEL 92.1.7 cells, while the BMP signaling inhibitor LDN-193189 also demonstrated dose dependence in stimulation of proliferation (p<0.001). Apoptosis of HEL 92.1.7 cells was slightly affected by BMP2 and LDN-193189. Summary/Conclusion: Our results show that BMP2 has anti-fibrotic activity that is antagonistic to TGF-β. This indicate that BMP2 may modify the TGF-β signaling pathway.
Diffuse Decreased Blood Flow in the Right Lung: Mitral Regurgitation-induced Pulmonary Hypertension
Authors: Akihito Okazaki, Keiko Kinuya, Manabu Fujimoto
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Diffuse Decreased Blood Flow in the Right Lung: Mitral Regurgitation-induced Pulmonary Hypertension." American Journal of Respiratory and Critical Care Medicine, 206(6), pp. 775–776
P1681: FXI LEVELS AS INDEPENDENT RISK FACTOR FOR THROMBOSIS/OBSTETRIC EVENTS IN PATIENTS WITH ANTIPHOSPHOLIPID ANTIBODIES
Authors: M. E. De La Morena-Barrio, J. Pagan, A. Miñano, V. Roldan, A. Lopez-Arribas, J. Lozano, M. J. Hernandez-Vidal, I. de la Morena-Barrio, V. Vicente, M. L. Lozano, M. T. Herranz, J. Corral
Journal: HemaSphere (2022)

Background: Antiphospholipid antibody (aPL) is the most important acquired thrombophilia. Thrombotic risk assessment in these patients must be improved by evaluating new biomarkers. FXI is an excellent candidate, as it is a phospholipid binding protein involved in coagulation and inflammation, high FXI levels increases the risk of thrombosis, and FXI deficiency protects against thrombosis. Aims: To evaluate the prognostic role of FXI in aPL Methods: Cross-sectional and observational study of aPL patients ≥ 18 years recruited in a single center. Clinical, analytical, and epidemiological variables were analyzed. Biochemical and functional evaluation of plasma FXI was done by western blotting and two coagulation assays (FXI:C). Molecular analysis of F11 gene (sequencing and MLPA) was done in cases with FXI deficiency. Primary study outcome was to identify a role for FXI levels in the thrombotic risk of aPL patients. Results: 194 participants were included, 82 asymptomatic aPL (AaPL) and 112 with antiphospholipid syndrome (APS). FXI:C values were significantly higher in patients with APS than AaPL. Cases with high FXI (>150%) were 14 times higher in the APS group (OR= 14,95; 95% CI: 1.95-114.83; p= 0.009). In contrast, cases with FXI deficiency (<70%) were 4 times higher in the AaPL group (OR= 4.93; 95% CI: 1.31-18.54; p= 0.018). FXI deficiency in aPL may be caused by genetic defects, but it is mainly caused by an inhibitor. Summary/Conclusion: This is the first study showing a prognostic role of FXI levels in patients with aPL. High levels increase the risk of APS while deficiency, either congenital or acquired by the aPL, protects against thrombosis.
The Effectiveness of 6 versus 12 Months of Dialectical Behavior Therapy for Borderline Personality Disorder: A Noninferiority Randomized Clinical Trial
Authors: Shelley F. McMain, Alexander L. Chapman, Janice R. Kuo, Katherine L. Dixon-Gordon, Timothy Henry Guimond, Cathy Labrish, Wanrudee Isaranuwatchai, David L. Streiner
Journal: Psychotherapy and Psychosomatics (2022)

Evidence-based psychotherapies for borderline personality disorder (BPD) are lengthy, posing a barrier to their access. Brief psychotherapy may achieve comparable outcomes to long-term psychotherapy for BPD. Evidence is needed regarding the comparative effectiveness of short- versus long-term psychotherapy for BPD.The aim was to determine if 6 months of Dialectical Behavior Therapy (DBT) is noninferior to 12 months of DBT in terms of clinical effectiveness.This two-arm, single-blinded, randomized controlled noninferiority trial with suicidal or self-harming patients with BPD was conducted at two sites in Canada. Participants (N = 240, M (SD)age = 28.27 (8.62), 79% females) were randomized to receive either 6 (DBT-6) or 12 months (DBT-12) of comprehensive DBT. Masked assessors obtained measures of clinical effectiveness at baseline and every 3 months, ending at month 24. DBT-6 and DBT-12 were outpatient treatments consisting of weekly individual therapy sessions, weekly DBT skills training group sessions, telephone consultation as needed, and weekly therapist consultation team meetings.The noninferiority hypothesis was supported for the primary outcome, total self-harm (6 months: margin = -1.94, Mdiff [95% CI] = 0.16 [-0.14, 0.46]; 12 months: margin = -1.47, Mdiff [95% CI] = 0.04 [-0.17, 0.23]; 24 months: margin = -1.25, Mdiff [95% CI] = 0.12 [-0.02, 0.36]). Results also supported noninferiority of DBT-6 for general psychopathology and coping skills at 24 months. Furthermore, DBT-6 participants showed more rapid reductions in BPD symptoms and general psychopathology. There were no between-group differences in dropout rates.The noninferiority of a briefer yet comprehensive treatment for BPD has potential to reduce barriers to treatment access.
PB2288: THE ABO SYSTEM POLYMORPHISM IN ALGERIAN BLOOD DONORS
Authors: F. talbi, D. damerdji
Journal: HemaSphere (2022)

Background: knowledge of the prevalence of ABO-Rhesus globular antigens ensures the stock of the blood bank allows the rational use of blood and its derivatives. Aims: assess the phenotypic frequencies of the ABO, Rhesus (D, C, c, E, e) and Kell systems in our population Methods: ambidirectional study over 11 years (2008-2018), n= 10,977 voluntary blood donations in 08 establishments. Bio-rad® reagents used for ABO, RH, K. Results: the number of blood donations is stable according to the quarter, p=0.25 (NS). The average age =34 years ±9.75 [18-71]. The most represented age group = 21-30 years: HR =1.94, p=.000 (s). Male donors n=9,778 (89%), sex ratio (M/F) =8.15. Compensation donors and occasional donors are evenly distributed between the sexes p=0.41 p=0.17 (NS) respectively. On the other hand, it is female donors who present themselves regularly for a blood donation as opposed to the male sex: (n=649 M, n=102 F): p=0.009 (S). We observed a trend increasing (different types of donations over time): HR=0.38, p=.000 (S). Blood donations are collected in 6 units, n=8136 by fixed teams and n=2839 by mobile fixed units. The phenotypic prevalences were: group O n=4666 (42.5%), group A (3825/35%), group B (1720/15.66%) and group AB (556/05%), the unidentified group n=210 cases. RHD (+) phenotype = 87%, Ag C (67%), c (65%) and e (36%), E (+) antigen = 18%, K (+) phenotype 10%. The predominant phenotype in our region is CceeK(-) then ccee-k(-) Image:Summary/Conclusion: The data of our study agree with those of previous studies carried out in different national centers. The use of these data allows us to better manage our stock of blood products and the formation of alloantibodies against minor antigens in polytransfused patients.
P429: CLONALLY RESOLVED SINGLE-CELL MULTI-OMICS IDENTIFIES LEUKEMIA SURFACE ANTIGENS
Authors: A. K. Merbach, S. Beneyto-Calabuig, J.-A. Kniffka, C. Szu-Tu, C. Rohde, M. Antes, M. Janssen, A. Waclawiczek, J. J. M. Landry, V. Benes, J. Anna, M. Brough, B. Besenbeck, J. Felden, S. Bäumer, M. Hundemer, T. Sauer, C. Pabst, M. Scherer, S. Raffel, L. Velten, C. Müller-Tidow
Journal: HemaSphere (2022)

Background: At the time of diagnosis, AML is a highly heterogeneous disease, usually consisting of various epigenetically and genetically distinct pre-leukemic, as well as leukemic subclones of various maturation stages that coexist in a competitive, or even cooperative manner. This clonal heterogeneity and, in particular, the strong resemblance of leukemic cells with their healthy counterparts presents a significant challenge in the identification of cancer specific gene expression and surface markers, both prerequisites for the development of targeted therapies. Existing approaches to add clonal resolution to droplet-based single-cell RNAseq data use qualitative information available from calls of individual mitochondrial or genomic single nucleotide variants as well as copy number variants. These single cell mutational calls, however, cannot be taken at face value, but need to be analysed through appropriate statistical methods, which are currently missing. Aims: Here we aimed at developing a novel method, CloneTracer, to add clonal resolution to new or existing human single-cell transcriptomic or multiomic datasets to ultimately allow identification of leukemia surface antigens through intra-sample comparison of cancerous and healthy cells of matched differentiation state. Methods: CloneTracer amplifies mitochondrial and selected nuclear SNVs, infers copy number variation, and estimates clonal hierarchies and identities through a Bayesian model that accounts for the noise properties of single-cell RNA-seq data. Results: Through combination of clonal identities with information on surface markers at single cell resolution, CloneTracer identified novel leukemia markers that enabled quantification of the leukemic burden in clinical specimens and enrichment for leukemic or healthy cells by FACS. Image:Summary/Conclusion: In summary, our data illustrate the benefits of clonally resolved single cell multi-omics for identifying cancer specific surface antigens and potential druggable targets by intra-patient comparisons.
PB2013: TECLISTAMAB COMPARED WITH REAL-WORLD THERAPIES IN PATIENTS WITH TRIPLE-CLASS EXPOSED RELAPSED/REFRACTORY MULTIPLE MYELOMA
Authors: A. Krishnan, A. K. Nooka, A. Chari, A. Garfall, T. Martin, S. Nair, X. Lin, K. Qi, A. Londhe, L. Pei, E. Ammann, R. Kobos, J. Smit, T. Parekh, M. Slavcev, S. Usmani
Journal: HemaSphere (2022)

Background: Teclistamab is a B-cell maturation antigen × CD3 bispecific antibody that promotes T cell activation by redirecting CD3+ T cells, resulting in lysis of BCMA-expressing myeloma cells. MajesTEC-1 (NCT04557098) is an open-label, single-arm, phase 1/2 trial of teclistamab in patients with relapsed/refractory multiple myeloma (RRMM) who had received at least 3 prior lines of therapy (LOT) and were triple-class exposed (TCE) to a proteasome inhibitor, an anti-CD38 monoclonal antibody, and an immunomodulatory agent. Aims: Because MajesTEC-1 did not include a control arm, comparative effectiveness of teclistamab versus treatment regimens using an external control arm from a real-world database was evaluated. Methods: The external control arm was created using eligible patients in the nationwide Flatiron Health multiple myeloma database, which was derived from de-identified electronic health records. Patients comprising the external control arm had received ≥3 prior LOT, started a new LOT per physician’s choice after triple-class exposure between January 2011 and August 2021, and met key MajesTEC-1 eligibility criteria. Individual patient data were included from patients who had been treated with 1.5 mg/kg weekly teclistamab in the MajesTEC-1 at the Sep 7, 2021 clinical cutoff. Imbalances in baseline covariates of prognostic significance (refractory status, number of prior LOT, progression on last LOT, International Staging System stage, cytogenetic risk, time since diagnosis, age, and hemoglobin), were adjusted by using inverse probability of treatment weighting (IPTW). Progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) were outcomes of interest, and were analyzed as time-to-event data utilizing IPTW adjusted Kaplan-Meier estimates and a weighted Cox proportional hazards model. Several sensitivity analyses were also performed. Results: The two cohorts were comparable for baseline characteristics after IPTW. Teclistamab improved PFS (hazard ratio [HR] 0.43; 95% confidence interval [CI] 0.32–0.59; P<0.0001), TTNT (HR 0.42; 95% CI 0.31–0.58; P<0.0001), and OS (HR 0.73; 95% CI 0.48–1.09; P=0.13) compared with real-world treatments. Sensitivity analyses showed results were also consistent with these findings. Summary/Conclusion: In patients with TCE RRMM who received at least 3 prior LOT, teclistamab showed improved effectiveness for PFS, TTNT, and OS versus real-world treatments, highlighting the therapeutic potential of teclistamab for patients with RRMM.
PB2321: A COMPLEX GENOTYPE THAT TRANSLATES INTO A BLEEDING PHENOTYPE
Authors: L. Fonseca, F. Martins Pereira, A. Brito, F. Lobo, M. Costa
Journal: HemaSphere (2022)

Background: Epistaxis is one of the most common complaints at emergency room and is recurrent among children. Most cases are of benign origin. Trauma, inflammation, vascular alterations, drugs or coagulopathies are the most frequent causes. In this latter case, it may be the first or even the only symptom. Aims: To describe a clinical case. Methods: A 9-year-old girl was referred to a coagulopathies specialist due to frequent and profuse epistaxis and gingivorrhagias. She had no bleeding complication during tooth extractions or vaccination. In family history, only her father and brother had recurrent episodes of epistaxis. No surgical history or medication were reported. The results of coagulation screening tests were: prolonged prothrombin time (PT) of 14.2 seconds, normal activated partial thromboplastin time (aPTT) of 34.2 seconds and low fibrinogen levels (1.8 g/L). The initial study also included a complete blood count and C-reactive protein, which were normal. Coagulation factor levels were measured and FVIII and FVII were normal, but FV was slightly decreased (41%). The VWF:Ag was 80.5% and VWF:Rco was 79.3% (VWF:RCo/VWF:Ag ratio 0,98). Because of the reduced plasma levels of FV, genetic tests were required. A panel of 43 genes was made in Next-Generation Sequencing (NGS). Results: NGS showed 3 genetic alterations: functional polymorphism on F5 gene associated with decreased FV levels; mutation in heterozygosity on VWF gene (autosomal dominant variant) characterized by increased affinity of VWF for platelet GPIBa, suggestive of von Willebrand Disease (VWD) type 2B; mutation in heterozygosity on NBEAL2 gene associated with macrothrombocytopenia. Summary/Conclusion: The study in this patient suggests that she has VWD type 2B. Although, the co-inheritance of the other 2 variants may be contributing to the patient hemorrhagic phenotype. Additional studies are essential to elucidate the genotype-phenotype correlation.
PB2245: CLINICAL CHARACTERISTICS AND RISK FACTORS OF ANEMIA IN PATIENTS WITH SYSTEMIC SCLEROSIS FROM THE PKUPH-SSC COHORT
Authors: Z. Li, D. Xu, T. Li, R. Mu
Journal: HemaSphere (2022)

Background: Systemic sclerosis (SSc) is a heterogeneous disease with diverse clinical phenotypes. Anemia has been implicated as an independent prognosis factor for mortality and organ complications in systemic sclerosis (SSc). Aims: To determine the characteristics of SSc patients with anemia in a population of patients from Peking University People’s Hospital SSc cohort (PKUPH-SSc), and associated risk factors. Methods: Patients were recruited from PKUPH-SSc between January, 1999 and January, 2020. The diagnosis of anemia was based on the reduced hemoglobin (Hb) concentrations (<120g/L for female and <130g/L for male) during follow-up. The demographics, clinical characteristics, laboratory parameters, autoantibodies and medication were collected. Logistic regression analysis and Cox regression analysis was applied to identify the risk factors independently associated with anemia in SSc. Results: A total of 302[Office1] patients were enrolled in PKUPH-SSc cohort, 150 (49.8%) patients developed anemia, containing more female (n=136, 90.7%) [Office2] patients. Normocytic-mild anemia[Office3] (n=115, 76.7%) was the most common type of anemia in SSc. According to the age-adjusted logistic regression analysis, gender of female (OR=4.77, 95%CI 2.09-10.92, p<0.001), SSc with overlap syndrome (OR=3.42, 95%CI 1.55-7.53, p=0.002), severe skin thickness (OR=3.04, 95%CI 1.44-6.41, p=0.004), ESR elevation (OR=2.22, 95%CI 1.20-4.11, p=0.011), CRP elevation (OR=2.20, 95%CI 1.03-4.69, p=0.042) and hypocomplementemia (OR=3.58, 95%CI 1.90-6.75, p<0.001) were independent risk factor determining the SSc patients with anemia[Office4]. In addition, as shown in figure, age at onset ≥ 49 years (HR=2.54, 95%CI 1.51-4.27, p<0.001) and SRC (HR=3.27, 95%CI 1.37-7.79, p=0.008) were proved to be the independent predictors to determine the 20-year incidence of anemia in SSc, while positive anti-centromere proteins (HR=0.42, 95%CI 0.24-0.76, p=0.003) seemed to be a protective factor. In terms of anemia subgroups, positive anti-Ro52 was a potential risk factor for microcytic anemia, but a protective factor for normocytic anemia. Summary/Conclusion: Anemia is associated with distinct clinical behaviors and disease progression in SSc. Age at disease onset ≥ 49 years, negative anti-centromere proteins antibody and SRC were independent predictors for 20-year incidence of anemia in SSc patients. Monitoring anemia in these patients was a potential management to evaluate the disease progression of SSc.
PB1871: PROGNOSTIC SIGNIFICANCE OF THE NOTCH1 GENE MUTATION AND OTHER LABORATORY FACTORS IN CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: D. Krauchanka, S. Arcady, M. Viktor
Journal: HemaSphere (2022)

Background: An important stage in the management of patients with CLL is the prediction of the course of the disease in order to assess the need for an earlier onset of therapy and the use of alternative therapy on an individual basis, depending on the detectable prognostic markers. Aims: To determine the interrelationship of clinical-laboratory (as well as molecular-genetic) prognostic markers with various courses of CLL. Methods: We have examined 107 patients diagnosed with CLL in SI «RRC RM&HE» from 2017 to 2020. This cohort was divided into 2 groups: 1st group (49 patients) without signs of progression of CLL, and the 2nd group (58 patients) with clinical signs of disease progression after 3 years of observation. The median age in the 1st group was 61 years, in the 2nd - 62 years. The material for the study was venous blood. To determine the immunophenotype of tumor cells we used the flow cytofluorimeter FacsCanto II. Detection of β2-mg, TK and TPA was performed using the chemiluminescent analyzer. To determine the mutations of the NOTCH1 gene (34th exon), SSCP-PCR was used, followed by direct sequencing of DNA samples with conformational polymorphism. We used nonparametric statistics methods calculated in the Statistica 10.0. Statistically significant differences were considered for p<0.05. Results: Patients in group 1 differed from patients in group 2 in levels of β2-mg-1.8 and 3.5 μg/L (p<0.001) and LDH-220 and 326 U/L (p<0.002). TK levels (p<0.001) and TPA (p<0.011) were also significantly higher in group 2 (7.7 and 49.8 IU/L) compared with patients in group 1 (4.2 and 34.3 IU/L). According to immunophenotyping data, statistically significant differences were obtained on the Zap70 marker: in the 1st group the median was 10.1%, in the 2nd group - 21.6%. As a result of molecular genetic analysis, mutations in the NOTCH1 gene were identified in 14 patients. It was found that patients without progression at the time of inclusion in the study in the presence of mutations in the NOTCH1 gene had a statistically significantly shorter progression-free survival (mean 33.4 months (95% CI [22.0-44.8]) compared with patients without mutations (59.2 months (95% CI [54.1–64.3]) (p=0.018), which indicates the association of NOTCH1 mutations with a poor prognosis for disease progression in patients with CLL. Summary/Conclusion: It was found that markers such as LDH, β2-mg, TK, TPA, ZAP70 and NOTCH1 gene mutation have certain prognostic significance, which was confirmed by comparing their levels in patients with and without CLL progression after 3 years of observation. We can use NOTCH1 gene mutation as an additional factor in predicting the course of CLL. Knowledge of reliable prognostic markers may allow to initiate in-time treatment or to adjust therapy for patients with high-risk CLL with a probable increase in their life span.